期刊
PROTEIN & CELL
卷 11, 期 10, 页码 740-770出版社
OXFORD UNIV PRESS
DOI: 10.1007/s13238-020-00762-2
关键词
aging; single-cell sequencing; blood; COVID-19; immune cells
类别
资金
- National Key Research and Development Program of China [2018YFC2000100, 2017YFA0103304, 2017YFA0102802, 2018YFA0107203, 2017YFA0105804]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010000]
- National Natural Science Foundation of China [81670897, 81625009, 91749202, 81861168034, 81921006, 31671429, 91949209, 91749123, 81671377, 81822018, 81870228, 81922027, 81701388, 81601233]
- Program of the Beijing Municipal Science and Technology Commission [Z191100001519005]
- Beijing Natural Science Foundation [Z190019]
- Beijing Municipal Commission of Health and Family Planning [PXM2018_026283_000002]
- Advanced Innovation Center for Human Brain Protection [3500-1192012]
- Key Research Program of the Chinese Academy of Sciences [KFZDSW-221]
- K.C. Wong Education Foundation [GJTD-2019-06, GJTD2019-08]
- Youth Innovation Promotion Association of CAS [2016093]
- State Key Laboratory of Membrane Biology
- State Key Laboratory of Stem Cell and Reproductive Biology
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
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